Variants of the caries-associated oral microbe Streptococcus mutans will be selected following chemical nutagenesis of virulent strains. Mutants will be selected by replica plating, batch enrichment, or growth on selective media. The variant types sought will include cells with defects in: glucan synthesis, plaque formation, agglutination, acidogenesis, aciduricity, internal polysaccharide synthesis/degradation, dextranase, levanase, invertase, and phosphate accumulation. Following in vitro characterization, gnotobiotic or specific pathogen-free rats will be infected with a mutant type or suitable controls, maintained on a caries conducive diet, sacrificed, and scored for the extent of smooth surface and pit-and-fissure decay. Other related studies will include the purification of glucosyl transferase enzyme profiles using affinity chromatography. A comparison will be made between the wild type and plaque formation-defective variants. Also, in vitro and/or in vivo transformation will be undertaken using a competent non-cariogenic streptococcal recipient and virulent S. mutans donor. The genetic markers of interest will be the ability to form a tenacious colonial deposit on a surface or the acquisition of antibiotic resistance. Biochemical studies will center on the regulation of carbon flow from sucrose to biosynthetic and catabolic cell prossesses such as IPS synthesis and lactate production. The enzymes of special interest are invertase, mannitol-l-phosphate dehydrogenase, glucose pyrophosphorylase, glutamate dehydrogenase, and phosphoenolpyruvate carboxylase, and the resultant balances struck among their functions. From the genetic approach, which is designed to establish the relative importances of diverse caries-associated traits, and from the biochemical perspective of the control of the growth and metabolism of a pathogenic microbe, a better understanding of the widespread disease -- tooth decay -- should emerge. BIBLIOGRAPHIC REFERENCES: Tanzer, J., M. Freedman, R. Eifert, F. Woodiel, and L. Rinehimer. Association of Streptococcus mutans' virulence with intracellular polysaccharide synthesis. Int. Assoc. Dent. Res. Miami Mtg. (1976). Freedman, M. and A. Coykendall. 1975. Variation in internal polysaccharide systhesis among Streptococcus mutans strains. Infect. and Immun. 12:475-479.